Treatment of segmental bone loss remains a major challenge. Traditional techniques (e.g., the use of autografts, allografts, etc.) and newer techniques (e.g., recombinant human bone morphogenetic protein) have well-established performance limitations and patient morbidity, as well as safety concerns.
Suitable bone graft materials should ideally: (i) match the mechanical properties of healthy bone in terms of stiffness, strength and toughness to prevent stress shielding and failure; (ii) be biocompatible/osteoinductive/osteoconductive, and (iii) degrade and resorb over time so healthy bone can take over. No known non-autogenous materials exist that can suitable fulfill these three requirements simultaneously. Titanium, which is widely used for orthopedic bone implants, is generally too stiff and does not resorb over time. Calcium phosphate formulations are alternatively used because they are biocompatible and degradable, but they tend to be too stiff and brittle. Collagen-based synthetics can provide a favourable environment for bone regeneration, but are known to give poor structural support.
In addition to the requirements listed above, segmental bone defects in certain regions of the body present additional challenges because their treatment requires grafts with complex three-dimensional geometries.
Some existing materials which are biocompatible and degradable are approved by the U.S. Food and Drug Administration (FDA) for use as implants. They have often served as ingredients to fabricate hybrid bone substitute materials. While certain materials show encouraging results, the range of their applicability is often limited by their fragility. The structure of these biomaterials is typically poorly controlled, and strengthening and toughening mechanisms have not been systematically exploited and optimized.
Furthermore, the fabrication of suitable bone graft materials for large gaps or large defects has been a longstanding challenge. Historically, known materials have only been effective for non-structural bony defects or extremely small and simple segmental defects.